MEDLINE INDIA - GOOD CLINICAL PRACTICE GUIDELINES

APPENDIX V

ESSENTIAL DOCUMENTS FOR THE CONDUCT OF A CLINICAL TRIAL

Essential Documents are those documents which individually and collectively allow the evaluation of the conduct of a study and the quality of the data generated. These documents demonstrate the compliance (or otherwise) of the Investigator, Sponsor and Monitor with the Good Clinical Practice and with other applicable regulatory requirements.

Essential Documents are needed for Sponsor’s independent audit function and inspection by the Regulatory Authority.

The various Essential Documents needed for different stages of the study are classified under three groups:

1. before the clinical phase of the study commences,

2. during the clinical conduct of the study, and

3. after completion or termination of the study.

The documents may be combined but their individual elements should be readily identifiable.

Master files containing all documents pertaining to the study should be created at the beginning of the study, at the Investigator / Institution site, Sponsor’s office, Ethics committee’s office and the CRO’s office.

Legend :

I - Investigator / Institute, S - Sponsor, C - CRO,

E - IEC, NA - Not applicable

Title of Document		Purpose	Located in files of
			I	S	C	E
Before the Clinical Phase of the Trial Commences During this planning stage the following documents should be generated and should be on file before the trial formally starts
1	Investigator’s brochure	To document that relevant and current scientific information about the investigational product has been provided to the investigator	.yes	yes	yes	yes
2	Signed protocol and amendments, if any, and sample case report form(CRF)	To document investigator and sponsor agreement to the protocol/amendment(s) and CRF	yes	yes	yes	yes
3	Information given to trial subject - informed consent form (including all applicable translations)	To document the informed consent	yes	yes	yes	yes
4	- Any other written information	To document that subjects will be given appropriate information (content and wording) to support their ability to give fully informed consent	yes	yes	yes	yes
5	- Advertisement for subject recruitment (if used)	To document that recruitment measures are appropriate and not coercive	yes	yes	yes	yes
6	Financial aspects of the trial	To document the financial agreement between the investigator/institution and the sponsor for the trial	yes	yes	yes	yes
7	Insurance statement (where required)	To document that compensation to subject(s) for trial-related injury will be available	yes	yes	yes	yes
8	Dated, documented approval / favourable opinion of independent ethics committee (IEC) of the following: - protocol and any amendments - CRF (if applicable) - informed consent form(s) - any other written information to be provided to the subject(s) - advertisement for subject recruitment (if used) - Subject compensation (if any) - any other documents given approval / favourable opinion	To document that the trial has been subject to IEC review and given approval / favourable opinion. To identify the version number and date of the document(s)	yes	yes	yes	yes
9	Independent ethics committee composition	To document that the IEC is constituted in agreement with GCP	yes	yes	yes	yes
10	Regulatory authority(ies) authorisation / approval / notification of protocol (where required)	To document appropriate authorisation / approval / notification by the regulatory authority(ies) has been obtained prior to initiation of the trial in compliance with the applicable regulatory requirement(s)	yes	yes	yes	yes
11	Curriculum vitae and/or other relevant documents evidencing qualifications of Investigator(s) and Co-Investigator / Sub-Investigator(s)	To document qualifications and eligibility to conduct trial and/or provide medical supervision of subjects	yes	yes	yes	yes
12	Normal value(s) / range(s) for medical / laboratory / technical procedure(s) and/or test(s) included in the protocol	To document normal values and/or ranges of the tests	yes	yes	yes	NA
13	Sample of label(s) attached to investigational product container(s)	To document compliance with applicable labelling regulations and appropriateness of instructions provided to the subjects	yes	yes	yes	NA
14	Instructions for handling of investigational product(s) and trial-related materials (if not included in protocol or Investigator’s Brochure)	To document instructions needed to ensure proper storage, packaging, dispensing and disposition of investigational products and trial-related materials	yes	yes	yes	NA
15	Shipping records for investigational product(s) and trial-related materials	To document shipment dates, batch numbers and method of shipment of investigational product(s) and trial-related materials. Allows tracking of product batch, review of shipping conditions, and accountability	yes	yes	yes	NA
16	Certificate(s) of analysis of investigational product(s) shipped	To document identity, purity, and strength of investigational product(s) to be used in the trial	NA	yes	yes	NA
	Decoding procedures for blinded trials	To document how, in case of an emergency, identity of blinded investigational product can be revealed without breaking the blind for the remaining subject’s treatment	yes	yes	yes	NA
17	Master randomisation list	To document method for randomisation of trial population	NA	yes	yes	NA
18	Pre-trial monitoring report	To document that the site is suitable for trial (may be combined with Trial initiation monitoring report)	NA	yes	yes	NA
19	Trial initiation monitoring report	To document that the trial procedures were reviewed with the investigator and the investigator’s trial staff (may be combined with Pre-trial monitoring report)	yes	yes	yes	NA
Duration of Clinical Conduct of the Trial In addition to having on file the above documents, the following should be added to the files during the trial as evidence that all new relevant information is documented as it becomes available
20	Investigator’s brochure updates	To document that investigator is informed in a timely manner of relevant information as it becomes available	yes	yes	yes	yes
21	Any revision to: - protocol amendment(s) and CRF - informed consent form - any other written information provided to subjects - advertisement for subject recruitment(if used)	To document revisions of these trial related documents that take effect during trial	yes	yes	yes	yes
22	Dated, documented approval / favourable opinion of Independent ethics committee (IEC) of the following: - protocol amendment(s) - revision(s) of: - informed consent form - any other written information provided to subject - advertisement for subject recruitment(if used) - any other documents given approval / favourable opinion - continuing review of trial (where required)	To document that the trial has been subject to IEC review and given approval / favourable opinion. To identify the version number and date of the document(s).	yes	yes	yes	yes
23	Regulatory authority(ies) authorisations / approvals / notifications where required for: - protocol amendment(s) and other documents	To document compliance with applicable regulatory requirements	yes	yes	yes	yes
24	Curriculum vitae for new investigator(s) and / or sub- investigator(s)	To document qualifications and eligibility to conduct trial and/or provide medical supervision of subjects	yes	yes	yes	yes
25	Updates to normal value(s) / range(s) for medical / laboratory / technical procedure(s) / test(s) included in the protocol	To document normal values and ranges that are revised during the trial	yes	yes	yes	NA
26	Medical / laboratory / technical procedures / tests - certification or - accreditation or - established quality control and / or external quality assessment or - other validation (where required)	To document that tests remain adequate throughout the trial period	yes	yes	yes	NA
27	Documentation of investigational product(s) and trial-related material shipment	To document shipment dates, batch numbers and method of shipment of investigational product(s) and trial-related materials. Allows tracking of product batch, review of shipping conditions, and accountability	yes	yes	yes	NA
28	Certificate(s) of analysis for new batches of investigational products	To document identity, purity, and strength of investigational product(s) to be used in the trial	NA	yes	yes	NA
29	Monitoring visit reports	To document site visits by, and findings of, the monitor	NA	yes	yes	NA
30	Relevant communications other than site visits - letters - meeting notes - notes of telephone calls	To document any agreements or significant discussions regarding trial administration, protocol violations, trial conduct, adverse event (AE) reporting	yes	NA	yes	NA
31	Signed informed consent forms	To document that consent is obtained in accordance with GCP and protocol and dated prior to participation of each subject in trial. Also to document direct access permission	yes original	yes copy	yes copy	NA
32	Source documents	To document the existence of the subject and substantiate integrity of trial data collected. To include original documents related to the trials, to medical treatment, and history of subject	yes original	yes copy	yes copy	NA
33	Signed, dated and completed case report forms (CRF)	To document the existence of the subject and substantiate integrity of trial data collected. To include original documents related to the trial, to medical treatment, and history of subject	yes copy	yes copy	yes copy	NA
34	Documentation of CRF corrections	To document all changes / additions or corrections made to CRF after initial data were recorded	yes original	yes copy	yes copy	NA
35	Notification by originating investigator to sponsor of serious adverse events and related reports	Notification by originating investigator to sponsor of serious adverse events and related reports	yes	yes	yes	yes
36	Notification by sponsor and/or investigator, where applicable, to regulatory authority(ies) and IEC(s) of unexpected serious adverse drug reactions and of other safety information	Notification by sponsor and/or investigator, where applicable, to regulatory authorities and IEC(s) of unexpected serious adverse drug reactions and of other safety information	yes	yes	yes	yes
37	Notification by sponsor to investigators of safety information	Notification by sponsor to investigators of safety information	yes	yes	yes	yes
38	Interim or annual reports to IEC and authority(ies)	Interim or annual reports provided to IEC and to authority(ies)	yes	yes	yes	yes
39	Subject screening log	To document identification of subjects who entered pre-trial screening	yes	yes where required	yes where required	NA
40	Subject identification code list	To document that investigator / Institution keeps a confidential list of names of all subjects allocated to trial numbers on enrolling in the trial. Allows investigator/ Institution to reveal identity of any subject	yes	yes	yes	NA
41	Subject enrolment log	To document chronological enrolment of subjects by trial number	yes	yes	yes	NA
42	Investigational products accountability at the site	To document that investigational product(s) have been used according to the protocol	yes	yes	yes	NA
43	Signature sheet	To document signatures and initials of all persons authorised to make entries and / or corrections on CRFs	yes	yes	yes	NA
44	Record of retained body fluids/ tissue samples (if any)	To document location and identification of retained samples if assays need to be repeated	yes	yes	yes	NA
After Completion or Termination of the Trial After completion or termination of the trial, all of the documents identified should be in the file together with the following
45	Investigational product(s) accountability at site	To document that the investigational product(s) have been used according to the protocol. To documents the final accounting of investigational product(s) received at the site, dispensed to subjects, return by the subjects, and returned to sponsors	yes	yes	yes	NA
46	Documentation of investigational product destruction	To document destruction of unused investigational products by sponsor or at site	yes	yes	yes	NA
47	Completed subject identification code list	To permit identification of all subjects enrolled in the trial in case follow-up is required. List should be kept in a confidential manner and for agreed upon time	yes	yes	yes	NA
48	Audit certificate (if available)	To document that audit was performed	NA	yes	yes	NA
49	Final trial close-out monitoring report	To document that all activities required for trial close-out are completed, and copies of essential documents are held in the appropriate files	NA	yes	yes	NA
50	Treatment allocation and decoding documentation	Returned to sponsor to document any decoding that may have occurred	NA	yes	yes	NA
51	Final report by investigator to IEC where required, and where applicable, to the regulatory authority(ies)	To document completion of the trial	yes	yes	yes	yes
52	Clinical study report	To document results and interpretation of trial	yes	yes	yes	yes